Trafficking of Immune Cells

Blood flow to the heart often is interrupted during a heart attack or cardiac surgery. But when blood flow resumes, the heart may still falter. That's because collateral damage can occur as blood re-enters the heart, potentially slowing recovery and causing future cardiac troubles.

Researchers investigating this type of secondary heart damage have been stymied by the inability to see in real time how restoring blood flow leads to inflammation that can cause further injury.

The researchers say that the imaging technique, called intravital two-photon imaging, is a powerful tool for understanding the inflammation that occurs when blood flow to the heart is temporarily stopped and later restarted.

"Inflammation is quite common after a heart attack, open-heart surgery, heart transplants and in atherosclerosis, and it can severely hamper recovery and lead to death," says Doctor Daniel Kreisel. "But little is known about how inflammation ramps up in the heart. Now that we have the ability to see all the cellular players involved, we can begin to think about new therapeutic targets for treatment."

Two-photon imaging has been used to image other organs in living mice but never the heart. Scientists had assumed that the flutter of the beating heart, which pulses about 500 times a minute in a mouse, would blur any images of individual cells.

"No one thought we could get clear images of cells inside the beating heart," says Doctor Wenjun Li. "But the images we captured are incredibly rich in detail, right down to the level of single cells. We think the principles underlying inflammation in the mouse heart will be applicable to humans."

One advantage of two-photon microscopy is the ability to penetrate deep into tissue, allowing scientists to image cells in the heart tissue. Using the technique in mice that had undergone heart transplants or had a blood flow to the heart temporarily interrupted, the researchers saw that within minutes of restoring blood flow, specialised white blood cells, called neutrophils, rushed into the heart.

Neutrophils are known to be a key driver of inflammation but scientists had never seen the trafficking of immune cells as they move from the circulation into the heart muscle, where the cells formed large clusters that cause tissue damage.